Many proteins such as various antibodies, receptors and peptides that have specific binding activities can be included in human and non-human animal food products or supplements as well as pharmaceutical and cosmetic products to achieve various beneficial effects by binding to the target biomolecules. However, the use of such proteins has been limited because many of the manufacturing processes for the above products involve a heating step during which the specific binding activities of the proteins are destroyed.
The above problem is well illustrated in the animal feed industry. Pelleted feed is preferred over feed mash because it has the advantage of less feed waste and improved ease of handling (Steven Leeson and John Summers, Commercial Poultry Nutrition (2nd ed.), p. 99, 1997, University Books, Guelph, Ontario, Canada). In addition, for the same amount of feed consumed, animals tend to spend less time and less energy eating pellets than feed mash, leading to higher feed efficiency (Leeson and Summers, p. 99). Pelleted feed is conventionally produced in pellet mills. To form pelleted feed, feed mash is first treated with steam and then passed through a die under pressure to form pellets (Leeson and Summers, p. 98). The pellets are then cooled quickly and dried by forced air. For the past twenty years, the temperature at which animal feed is pelleted has been raised from 71° C. to as high as 99° C. (Mike Coelho, Vitamin Stability in Premixes and Feeds: a Practical Approach, Proceedings of the BASF Technical Symposia, pp. 99-126, p. 104, May 25, 1994, Indianapolis, Ind.). Other methods available for processing feed mash, such as the extrusion method, the expander and compacter methods, and the thermal cooking method, all employ even higher temperatures than the steam pelleting method (Steven Leeson and John Summers, pp. 99-100, 1997). For example, the extrusion method which has been used to produce various pet foods and dry cereal snack foods employs a temperature of 121° C. to 149° C. (Mike Coelho, p. 100, 1994). Although various antibodies such as anti-phospholipase A2 (PLA2) and anti-CCK antibodies can be included in animal feed to promote animal growth and feed efficiency, the use of these antibodies have been limited to feed mash because they do not survive the high temperatures of the pelleting and extrusion processes. IgG is denatured at a temperature of 70° C. (Hajime Hatta et al., Biosci. Biotech. Biochem. 57:450-454, 1993).
Agents and methods that can heat-stabilize proteins and their binding activities at relatively high temperatures are desirable in the art.